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Background and ObjectivesMyasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG.MethodsIn this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II–Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available atclinicaltrials.gov/ct2/show/NCT02473965.ResultsThe primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated.DiscussionIn this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different.Trial Registration InformationThe trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) andclinicaltrials.gov(identifierNCT02473965).Classification of EvidenceThis study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

ObjectiveTo evaluate the safety and efficacy of efgartigimod in patients with generalized myasthenia gravis (MG) enrolled in the ADAPT+ long-term extension study.BackgroundTreatment with efgartigimod, a human IgG1 antibody Fc-fragment that blocks neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in MG-specific outcome measures in the ADAPT phase 3 clinical trial. All patients who completed ADAPT were eligible to enroll in its ongoing open-label, 3-year extension study, ADAPT+.Design/MethodsEfgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. Efficacy was assessed during each cycle utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales.ResultsNinety-one percent of ADAPT patients (151/167) entered ADAPT+. As of February 2021, 106 AChR-Ab+ and 33 AChR-Ab– patients had received at least 1 dose of open-label efgartigimod (including 66 ADAPT placebo [PBO] patients). The mean (SD) study duration was 363 (114) days, resulting in 138 patient-years of observation. Similar incidence rates per patient year (IR/PY) of serious adverse events were seen in ADAPT (efgartigimod: 0.11; placebo: 0.29) compared to ADAPT+ (0.25). Five deaths (acute myocardial infarction, COVID-19 pneumonia/septic shock, bacterial pneumonia/MG crisis, malignant lung neoplasm, and unknown [multiple cardiovascular risk factors identified on autopsy]) occurred; none were considered related to efgartigimod by the investigator. AEs were predominantly mild or moderate. CMI was observed in AChR-Ab+ patients during each cycle (up to 10 cycles) at magnitudes comparable to improvements observed at week 3 of cycle 1 (mean[SE] improvements: MG-ADL, –5.1[0.34]; QMG, –4.7[0.41]). Clinical improvements mirrored maximal reductions in total IgG and AChR-Abs across all cycles.ConclusionsThis analysis suggests the efficacy of long-term treatment with efgartigimod was consistent across multiple cycles. No new safety signals were identified, despite being conducted before vaccine availability during the COVID-19 pandemic.

ObjectivesTo estimate patient-acceptable symptom state (PASS) cut points for myasthenia gravis (MG) health scales.MethodsWe conducted an electronic survey that included the Myasthenia Gravis Impairment Index (MGII), EuroQol 5-Dimension (EQ5D), and a simple PASS question. PASS-anchored thresholds were estimated for the MGII questionnaire through receiver operating characteristic curves. We used the MGII PASS cut point in a validation cohort of 257 patients to estimate PASS thresholds for other clinically relevant health scales such as the Quantitative Myasthenia Gravis Scale (QMGS), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Composite (MGC), and Myasthenia Quality of Life (MG-QoL15).ResultsOne hundred twenty-four of ≈250 invited patients answered the electronic survey (49% response rate), and 80 considered their current symptom state acceptable (PASS-positive). They had lower MGII scores than PASS-negative patients (7.76 ± 9.37 vs 25.0 ± 13.7, p < 0.0001) and better EQ5D scores (0.86 ± 0.17 vs 0.69 ± 0.18, p < 0.0001). The MGII questionnaire threshold for PASS was ≤10 points. With the use of this threshold in an independent dataset of 257 patients, all patients in remission or minimal manifestation status were PASS-positive. In addition, some patients in Classes I, II, and IIIA also achieved PASS status. PASS thresholds for the QMGS, MG-ADL, MGC, and MG-QoL15 were ≤7, 2, 3, and 8 points, respectively.ConclusionsWe have estimated thresholds for commonly used myasthenia health scales reflecting patient-acceptable states in patients with MG. These thresholds indicate a global state of well being, rather than a change in scores, or being better. Therefore, PASS thresholds can be used as secondary endpoints for myasthenia research.

In the current proof-of-concept study, we aimed to examine the sensitivities and specificities of previously reported normal values for muscle ultrasound thickness in amyotrophic lateral sclerosis.Muscle ultrasound was performed in 65 healthy control subjects and 91 amyotrophic lateral sclerosis patients using a standardized assessment of eight relaxed muscles and four contracted muscles. Normal values for muscle thickness were determined as values above the 5th percentile stratified by age and gender using the weighted average method. Sensitivity for amyotrophic lateral sclerosis diagnosis was determined for muscles with and without the addition of muscle contraction.Amyotrophic lateral sclerosis patients showed reduced muscle sum thickness both in relaxed and in contracted states compared with control subjects. Muscle ultrasound of muscles with and without contraction showed excellent diagnostic accuracy for differentiating amyotrophic lateral sclerosis patients from control subjects (area under curve = 0.96, sensitivity: 93%-95%, specificity: 84-87). Muscle ultrasound sensitivity was lower within 6 months of symptom onset (83%) compared with longer disease duration (92%).Quantitative sonographic assessment of muscle thickness can be complementary in the diagnosis of amyotrophic lateral sclerosis with excellent accuracy for differentiating patients from healthy subjects, and might be useful in other neuromuscular disorders, although additional studies are required.

Objectives Multifocal motor neuropathy (MMN) is a treatable autoimmune polyneuropathy, which may prove challenging diagnostically in the setting of absent conduction blocks or advanced axonal loss. Relatively few studies have examined the role of ultrasound (US) in MMN. Methods Retrospective, cross-sectional study of patients with MMN who underwent peripheral nerve US. Charts were reviewed to extract clinical, sonographic, and electrophysiological data. Results Eleven patients with MMN underwent US between 2013 and 2015; of these 11 patients, 7 had ≥3 abnormal nerve segments, and 6 had ≥5 sites of increased cross-sectional area (CSA). There was moderate correlation between the degree of amplitude drop observed in the median and ulnar motor nerves, and CSA. Significant correlation between CSA and limb strength was only observed for the median nerve. Conclusions Peripheral nerve US shows promise as a diagnostic tool in MMN and may be helpful to distinguish MMN from motor neuron disease.

ObjectiveTo explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG).MethodsIn this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1–29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29–43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44–99). Primary endpoint: change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints: change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores; safety.ResultsForty-three patients were randomized (rozanolixizumab: 21 patients; placebo: 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo: QMG (LS mean: −1.8 vs −1.2; difference: −0.7; 95% UCL: 0.8; p = 0.221; not statistically significant), MG-ADL (LS mean: −1.8 vs −0.4; difference: −1.4; 95% UCL: −0.4), and MGC (LS mean: −3.1 vs −1.2; difference: −1.8; 95% UCL: 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab: 57%; placebo: 14%).ConclusionWhile change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422).Classification of evidenceThis study provides class I evidence that for patients with gMG, rozanolixizumab is well tolerated, but did not significantly improve QMG score.

Objective: To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG). Methods: We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody–positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living. Results: Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4–12 prednisone AUDTC when compared to placebo (difference MTX − placebo: −488.0 mg, 95% confidence interval −2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%). Conclusions: We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials. Classification of evidence: This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy.

Neuralgic amyotrophy is characterized by acute or subacute onset of shoulder and arm pain, followed by muscle atrophy and weakness, and variable sensory abnormalities. Historically, the site of inflammation has been localized to the brachial plexus, although the involvement of individual nerve branches has been well recognized.We describe ultrasound findings in two cases with a clinical presentation suggestive of neuralgic amyotrophy, involving individual peripheral nerves, correlating with clinical and electrophysiological findings.In the first case, selective fusiform enlargement of the left radial nerve in the proximal forearm is shown, whereas in the second case, fusiform enlargement of the left median nerve in the antecubital fossa is shown.These cases confirm that the site of nerve inflammation may lie outside the brachial plexus, keeping with previous reports, and suggests that peripheral nerve ultrasound imaging might aid in the diagnosis of neuralgic amyotrophy and exclude mimicking conditions.

This article discusses the clinical features, pathophysiology, and management of primary and secondary acquired immune axonal neuropathies.Although there are many collagen vascular disorders associated with vasculitic neuropathy, a quarter of cases have been described to be due to nonsystemic vasculitis of the peripheral nervous system. Enhanced surveillance and aggressive treatment of conditions such as cryoglobulin-related vasculitic neuropathy with cyclophosphamide, rituximab, and alfa interferons has led to improved morbidity and mortality, however, many cases of immune axonal acquired neuropathy are still associated with poor outcomes. Acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) are well-characterized variants of Guillain-Barré syndrome.Characterizing the clinical and electrophysiologic phenotype can help diagnose conditions such as nonsystemic vasculitic neuropathy, AMAN, AMSAN, and immune small fiber neuropathy, while careful evaluation of systemic features is key to identifying secondary immune axonal neuropathies such as vasculitic neuropathy related to collagen vascular disease. Additional research is needed to determine the exact immune pathogenesis and optimized treatment regimens for all acquired immune axonal neuropathies.

Diabetes mellitus has become a modern global epidemic, with steadily increasing prevalence rates related to lifestyle such that 27% of individuals aged 65 years or older have diabetes mellitus, 95% of whom have type 2. This article reviews the effects of diabetes mellitus on the neuromuscular system.Diabetes mellitus leads to diverse forms of peripheral neuropathy as the major neuromuscular complication. Both focal and diffuse types of neuropathy can develop, with the most common form being diabetic sensorimotor polyneuropathy. Small fibers are damaged early in the development of diabetic sensorimotor polyneuropathy and are not assessed by nerve conduction studies. Small fiber damage occurs even in the prediabetes stage. No disease-modifying therapy for diabetic sensorimotor polyneuropathy is available at this time, but this complication can be limited in patients who have type 1 diabetes mellitus with strict glycemic control; the same outcome is not clearly observed in patients who have type 2 diabetes mellitus. Recently, the evidence base for symptomatic treatments of painful diabetic sensorimotor polyneuropathy underwent systematic review. Effective evidence-based treatments include some anticonvulsants (eg, pregabalin, gabapentin), antidepressants (eg, amitriptyline, duloxetine), opioids (eg, morphine sulfate, oxycodone), capsaicin cream, and transcutaneous electrical nerve stimulation.This article reviews the increasing prevalence of diabetes mellitus and diabetic sensorimotor polyneuropathy and discusses recent consensus opinion on the objective confirmation needed for the diagnosis in the clinical research setting. The evidence from clinical trials shows that intensive glycemic control reduces prevalence of diabetic sensorimotor polyneuropathy in patients with type 1 diabetes mellitus, but variable outcomes are observed in patients with type 2 diabetes mellitus. Finally, despite the lack of disease-modifying treatment, effective evidence-based therapy can control painful symptoms of diabetic sensorimotor polyneuropathy.

To determine whether the quantitative myasthenia gravis score (QMGS) accurately represents disease severity in patients with myasthenia gravis (MG).One hundred thirty-five patients with MG from 2 previous randomized studies were included. QMGS correlation with the Myasthenia Gravis Foundation of America (MGFA) score, quality of life scale, acetylcholine receptor antibodies (AChRAbs), and electrophysiological parameters was studied.The QMGS showed a good correlation with the MGFA scale (r² = 0.54, P0.0001), jitter (rs = 0.40, P0.0001), and 15-item quality of life scale (rs = 0.41, P = 0.007) and was less well correlated with the 60-item myasthenia gravis-specific quality of life survey and other electrophysiological markers. No correlation was demonstrated with AchRAb titers, but AchRAb-positive patients had higher QMGS (14.2 ± 4.5) than AchRAb-negative patients (12.0 ± 3.7, P = 0.008).These results demonstrate that the QMGS is a valid marker for disease severity as shown by the MGFA scale, quality of life scale, and jitter, supporting the use of the QMGS as a primary outcome measure in clinical trials of MG.

Objective: Both IV immunoglobulin (IVIg) and plasma exchange (PLEX) are immunomodulatory treatments used to treat patients with myasthenia gravis (MG), but the choice of which treatment to administer to patients is limited due to lack of evidence from adequately powered, masked, randomized, standardized trials. Methods: We randomized 84 patients with moderate to severe MG defined as a Quantitative Myasthenia Gravis Score for disease severity (QMGS) of >10.5 and worsening weakness to IVIg (Gamunex®, Talecris Biotherapeutics) 1 g/kg/day for 2 consecutive days or PLEX (Caridian Spectra) 1.0 plasma volume exchanges for 5 exchanges. The patients were evaluated at day 14 after treatment for the primary efficacy parameter of change in QMGS and secondary clinical and electrophysiologic parameters and were followed for a total of 60 days. Results: Both IVIg and PLEX reduced the QMGS, and IVIg was comparable to PLEX in efficacy. The dropout rate was the same for both treatment arms and both treatments were well-tolerated. The presence of acetylcholine receptor antibodies and greater baseline disease severity predicted a better response to therapy. The postintervention status revealed that the same proportion of patients improved with treatment: 69% on IVIg and 65% on PLEX. The duration of improvement was similar with both treatments. Conclusions: IVIg has comparable efficacy to PLEX in the treatment of patients with moderate to severe MG. Both treatments are well-tolerated, and the duration of effect is comparable. Either treatment may be offered to patients depending on availability of resources. Classification of evidence: This study provides Class I evidence that IVIg and PLEX have comparable efficacy and are equally tolerated in adult patients with moderate to severe MG within 2 weeks of treatment.

Immunomodulation with plasma exchange is effective in preparing patients for thymectomy. Newer forms of immunomodulation, such as intravenous immunomodulation, require evaluation in this clinical setting.We conducted a retrospective chart review to determine if plasma exchange and intravenous immunoglobulin had comparable effectiveness in the preoperative preparation of patients with myasthenia gravis.The results show that intravenous immunoglobulin may have comparable efficacy in the preoperative preparation of patients with myasthenia gravis and that this therapy is a reasonable alternative to plasma exchange in this clinical setting.

Objective: We aimed to determine the effectiveness of IV immunoglobulin (IVIG) in the treatment of patients with myasthenia gravis (MG) and worsening weakness in a randomized, placebo-controlled, masked study. Methods: Fifty-one patients with worsening weakness due to MG were randomized to infusion with 2 g/kg of IVIG or an equivalent volume of IV dextrose 5% in water. The Quantitative Myasthenia Gravis (QMG) Score for Disease Severity, a validated clinical composite scale, was calculated by a masked observer at baseline and days 14 and 28. Results: In IVIG-treated patients, a clinically meaningful improvement in QMG Score for Disease Severity was observed at day 14 and persisted at day 28. The greatest improvement occurred in patients with more severe disease as defined by a QMG Score for Disease Severity greater than 10.5. Conclusion: This study provides level 1 evidence for the effectiveness of IV immunoglobulin in patients with worsening weakness due to myasthenia gravis.

The chronic autoimmune neuropathies are a diverse group of disorders, whose diagnosis and classification is based on the clinical presentations and results of ancillary tests. In chronic inflammatory demyelinating polyneuropathy, controlled therapeutic trials demonstrated efficacy for intravenous gamma-globulins, corticosteroids, and plasmaphereis. In multifocal motor neuropathy, intravenous gamma-globulins have been shown to be effective. In the other immune-mediated neuropathies, there are no reported controlled therapeutic trials, but efficacy has been reported for some treatments in non-controlled trials on case studies. Choice of therapy in individual cases is based on reported efficacy, as well as severity, progression, coexisting illness, predisposition to developing complications, and potential drug interactions.

Successful screening for neuropathy in patients with diabetes is available using the 10 g Semmes-Weinstein monofilament (Mid-Delta Health Systems, Inc., Belzoni, MS) (touch/pressure sensation) and the Neurothesiometer (Horwell Scientific, London, UK; vibration perception threshold). In healthy volunteers and patients with a broad range of diabetic sensorimotor neuropathy, we show that the predictive value of either test for diabetic sensorimotor neuropathy depends on the toe surface tested. These results establish the importance of standardized screening methods for diabetic sensorimotor neuropathy in the clinic and in clinical research trials.

We compared 42 myasthenia gravis (MG) patients with thymoma with 42 generalized MG patients without thymoma using a modified Osserman classification. The mean Osserman grades at diagnosis, 6 months, and 5 and 10 years post-thymectomy did not differ between groups. Our results indicate that thymoma is not a negative determinant for the long-term clinical outcome of MG.

Objective: The aim of this study was to evaluate the accuracy of different methods for evaluation of small fiber neuropathy (SFN) using intra epidermal nerve fiber density (IENFD) as the reference standard. Background IENFD is the current standard for evaluation of SFN but limited by invasiveness, expense and availability. Heat-induced neurogenic vasodilation by Laser Doppler Imaging (LDI), cold detection thresholds (CDT) and heat perception (HP) are noninvasive nerve function alternatives whose accuracy relative to morphological IENFD is unknown. Design/Methods: We performed a retrospective chart review of 75 patients suspected of having SFN at the Toronto General Hospital, University Health Network from 2008-2011. A detailed history and clinical examination, laboratory studies, nerve conduction studies (NCS), CDT, HP, LDI and IENFD were performed in all patients. We quantitatively compared the results of clinical evaluation including pain on the visual analogue scale (VAS), LDI, CDT and HP relative to IENFD for the diagnosis of SFN. Results: The mean IENFD was 7.52 +/- 4.12 with a median value of 7.59 and interquartile range of 4.64-10.91 (25% to 75%). 34.7% had abnormal IENFD and 65.3% had normal IENFD according to published criteria (normal defined as > 5.4 fibers/mm). Low-magnitude correlation was observed between IENFD and CDT (R2 =0.0812, p Conclusions: None of the objective measures reflected IENFD with very good diagnostic validity, but of these small fiber non-invasive methods, CDT had the highest level of accuracy, while we could not demonstrate acceptable performance of LDI. Alternate non-invasive methods for the determination of small fiber function or morphology are urgently needed. Disclosure: Dr. Ebadi has nothing to disclose. Dr. Perkins has nothing to disclose. Dr. Katzberg has received personal compensation for activities with Genzyme as a speaker and participant on an advisory board. Dr. Katzberg has received research support from Griffolds Biotherapeutics. Dr. Bril has received personal compensation for activities with Talecris Biotherapeutics as a consultant. Dr. Bril has received research support from Talecris Biotherapeutics.

Objective: To study if one or more FcR polymorphisms are correlated with response to IVIG treatment in Myasthenia Gravis (MG). Background Intravenous immunoglobulin (IVIG) is an effective treatment of moderate to severe MG, but only about 60% of patients respond to treatment, and there are no clear predictors of response. Fc receptors play an important role in the mechanism of action of IVIG, so genetic variation of these might predict response to treatment. Design/Methods: 71 patients who participated in previous studies of IVIG efficacy, and new patients treated with IVIG for worsening MG were included. Patients were considered responders if the quantitative myasthenia gravis score (QMGS) improved by > 3.5 units 14 days after treatment. Polymorphisms within the FCγR2A, FCγR2B, FCγR3A and FCγR3B (NA1/NA2) genes were genotyped and the rates of treatment response were analyzed by each genotype. Results: The mean age was 56 years and 59% of patients were female. The mean QMGS at baseline was 13.4 ± 4.5. The FCγR2B-232I/I genotype was significantly more common in responders (94%) compared to non-responders (77%) (p=0.04). None of the other polymorphisms were associated with response. Patients with the FCγR2B 232I/I genotype had a higher QMGS at baseline (14 ± 5) compared to heterozygotes (10 ±2, p=0.025) and higher baseline QMGS was associated with response to treatment (responders: 15 ± 5; non-responders 12 ±4, p=0.01). Multivariate logistic regression analysis showed that only the baseline QMGS independently predicted response to IVIG (p=0.036). Conclusions: We found that the FCγR2B I/I genotype is associated with greater disease severity in MG and this, in turn, predicts a better response to IVIG. Although confirmation of this finding in larger population samples is required, the finding that the wild type inhibitory FcγR predisposes to more severe disease suggests that the FCγR2B does not act by directly inhibiting the pathogenic antibodies in MG. Supported by: An unrestricted educational grant from Talecris Biotherapeutics for clinician-initiated research. Disclosure: Dr. Barnett Tapia has nothing to disclose. Dr. Grinberg has nothing to disclose. Dr. Ghani has nothing to disclose. Dr. Rogaeva has nothing to disclose. Dr. St George-Hyslop has received personal compensation for activities with Finnegan LLC. Dr. Katzberg has received personal compensation for activities with Genzyme as a speaker and participant on an advisory board. Dr. Katzberg has received research support from Griffolds Biotherapeutics. Dr. Bril has received personal compensation for activities with Talecris Biotherapeutics as a consultant. Dr. Bril has received research support from Talecris Biotherapeutics.

by ERIK STALBERG and JOZE V. TRONTELJ, 303 pp., ill., New York, Raven Press, 1994. $79.00 The second edition of this book is a welcome update of the standard reference text for anyone using single fiber electromyography (SFEMG) in the laboratory. This updated text continues the excellent traditions set in the first book by …